The clathrin assembly protein AP180 regulates the generation of amyloid-beta peptide.
The clathrin assembly protein AP180 regulates the generation of amyloid-beta peptide.
复制标题
网格蛋白组装蛋白 AP180 调节淀粉样β肽的生成。
DOI：
10.1016/j.bbrc.2009.05.050
复制
发表时间：
2009
影响因子：
3.1
通讯作者：
Yao,PamelaJ
中科院分区：
文献类型：
--
作者：
Wu,Fangbai;Matsuoka,Yasuji;Mattson,MarkP;Yao,PamelaJ
淀粉样蛋白-β多肽(A-β)的过量生产和细胞外积聚是阿尔茨海默病发病机制中的关键步骤。最近的数据表明，细胞内贩运在Aβ的生产中具有核心重要性。在这里，我们使用神经细胞系来检测两个结构相似的笼状蛋白组装蛋白，AP180和CAMPE。我们发现，RNA干扰介导的AP180基因敲除减少了Aβ1-40和Aβ1-42的产生，而Calm基因敲除对Aβ产生没有影响。因此，AP180是监督和调节淀粉样前体蛋白加工途径的交通管制员之一。我们的结果还表明，AP180和CAMP虽然在结构域结构和生化性质上相似，但实际上致力于神经元中不同的运输途径。
The overproduction and extracellular buildup of amyloid-β peptide (Aβ) are a critical step in the etiology of Alzheimer’s disease. Recent data suggest that intracellular trafficking is of central importance in the production of Aβ. Here we use a neuronal cell line to examine two structurally similar clathrin assembly proteins, AP180 and CALM. We show that RNA interference-mediated knockdown of AP180 reduces the generation of Aβ1–40 and Aβ1–42, whereas CALM knockdown has no effect on Aβ generation. Thus AP180 is among the traffic controllers that oversee and regulate amyloid precursor protein processing pathways. Our results also suggest that AP180 and CALM, while similar in their domain structures and biochemical properties, are in fact dedicated to separate trafficking pathways in neurons.